How Does EO Sterilization Work?
Ethylene oxide sterilization, commonly known as “EO,” uses ethylene oxide gas to kill microorganisms through a process called alkylation, a chemical reaction that adds alkyl groups to cellular components like proteins, RNA, and DNA. It inhibits the ability of the organisms to replicate, in turn disrupting cellular function, causing microorganisms to die.
The EO sterilization process has three main phases:
- Preconditioning/Humidification
Prior to the exposure to the EO gas, packaged products are brought to a controlled temperature and relative humidity (RH). Preconditioning hydrates microbial cells, causing their protective layers to swell, thus making them more susceptible to the alkylation process. Humidity is critical to facilitate EO sterilization, because the gas utilizes the moisture to penetrate and eliminate microorganisms.
- Sterilization
The preconditioned products are placed into a sterilization chamber. Sterilization chambers may be as large as a walk-in cooler or as small as 2 cubic feet, based on the size and needs of the product. Once in the chamber, products are exposed to a specific concentration of EO gas with set RH. The sterilization process usually takes several hours under the controlled conditions specified for RH, temperature and pressure.
- Aeration/Degassing
After sterilization, the devices are subjected to aeration. This is done by circulating filtered air over the load and out, to remove EO gas residuals from the product, reaching safe levels for human contact. This is the longest step in the EO cycle and is critical for the safety of the end user.
Biological Indicators
Biological indicators (BIs) are used to determine the success of sterilization. These are usually strips that have microorganisms on them that are placed within the load using process challenge devices (PCDs). These microorganisms are known to be difficult to kill with EO, making it the worst-case organism. An example of these microorganisms would be bacterial spore formers such as bacillus. A worst-case organism is used so that the manufacturer can be confident in their sterilization method. If the worst-case organism is killed, the more susceptible organisms should be as well.
Residual Testing
During the sterilization validation, the packaging will need to be tested for residual EO gas. Due to the toxic nature of EO gas, it’s imperative that the residual levels of EO meets regulatory requirements. If the EO levels are too high, the manufacturer would have to reconsider the concentration of EO used during sterilization or the dwell time.
What Materials Work With EO?
Many packaging materials, including plastics, are suitable for EO sterilization. It is just one of the reasons EO has remained in demand as a reliable, versatile and effective sterilization method for so long.
As the sophistication of medical devices has advanced with increasingly high-tech electronics, EO sterilization has maintained an advantage due to its low temperature process. It is compatible with:
- Textile papers like Tyvek®
- Medical grade papers
- Plastics: polypropylene, polyethylene, polycarbonate
What Materials Don’t Work With EO?
EO is incompatible with liquids, powders, foils (aluminum), Styrofoam and cellophane. And while electronics do well with EO sterilization, there are some serious risks that call for careful planning. EO is:
- Highly flammable
- Reactive to nucleophiles and aluminum
- Highly explosive
Once the risks have been examined, there is also a packaging requirement: all packaged medical devices that will be sterilized with EO must include a porous layer such as Tyvek®, or other permeable material.
Ethylene oxide sterilization subjects packaged goods to high moisture and vacuum conditions. If a product uses a film-to-film design without any permeability, it will be difficult for the moisture and EO gas to efficiently enter the packaging, and the packaging will burst during the aeration step. Inclusion of a porous material allows most of the packaging to remain non-porous while preventing burst failures.
It is possible that EO residual gas may be left behind, even with a small porous feature. This could be absorbed by the medical device. For this reason, if a device utilizes materials that absorb gasses, EO may not be suitable. By designing the device with non-absorbent materials, residual EO is not an issue. Performing post-sterilization micro-testing for concentrations of EO gas can confirm any residuals are within regulatory limits. If not, a root cause analysis may be required.
Is The Regulatory Spotlight On EO?
At least 50% of medical devices produced worldwide (20 billion annually) are sterilized using the EO method. Its long history has rendered reliable data that is widely accepted by the FDA for medical device manufacturers in meeting regulatory requirements for market approval.
Globally, industry also looks to ISO 11135, the (non-governmental) standard that authors requirements for developing, validating and controlling processes for EO sterilization.
Ethylene oxide was officially classified as a human carcinogen in 2016. Incidents at large sterilization facilities also led to public concerns over human health risks related to EO sterilization facilities. As such, practices have become strictly monitored. In addition to the FDA’s responsibilities, OSHA has tightened worker exposure limits and workplace practices. The Environmental Protection Agency (EPA) has also added regulations that affect many facets of production, sterilization and the critical need to ensure sterile medical devices.
With updated protections in place, and due to the lack of comparable sterilization methods, medical device customers have not shifted away from EO’s proven, cost effective and reliable results.
Every medical device sterilization method has risks, limitations and drawbacks that need to be addressed. For patient safety, sterility is the utmost requirement. While research continues in search of novel sterilization methods, for now, there is little to replace the benefits of EO sterilization.
Key Takeaways
Ethylene oxide (EO) sterilization remains one of the most widely used and trusted methods for medical devices due to its effectiveness and compatibility with many common packaging materials. The sterilization process relies heavily on controlled humidity and permeability to ensure microbial inactivation while preventing package failures. Material selection and package design are critical, as EO is incompatible with certain materials and requires a porous layer to safely manage pressure changes and gas removal. While EO faces increased regulatory scrutiny due to health and environmental concerns, it continues to be supported by extensive FDA-accepted data, continuing to be difficult to replace. As alternative sterilization technologies evolve, EO still offers a proven, cost-effective solution that meets today’s sterility and patient safety requirements.